Clostridium Difficile infection (CDI) can range in severity from asymptomatic to severe and life-threatening, especially among the elderly. People are most often infected in hospitals, nursing home, or other medical institutions, although CDI in the outpatient setting is increasing. Indeed, since 1996 the incidence of CDI has more than doubled resulting in up to three million cases each year in the United States and making CDI the most common bacterial cause of diarrhea in the United States. With the rising incidence, there is also a higher mortality associated with the disease. This mortality is related to at least two factors: (1) increasing virulence of the C. difficile strains; and (2) increasing host vulnerability.
The increase in occurrences of Clostridium Difficile associated diarrhea (CDAD) in hospitalized patients leads to high incremental costs for individuals who develop the disease. In the Veterans Administration Hospital System, over the last decade the cases of CDI have doubled to an estimated number of 10/1000 discharges for persons under 65 years of age and to 20/1000 discharges for persons over 65 years of age in the year 2004. Additional treatment costs due to CDI are estimated at $3600 per case. In addition, following treatment of the primary infection with antibiotics, the recurrence rate of the disease is very high. In the U.S., incremental costs per hospitalization were estimated to be $3,000 to $5,000 for primary infections and $13,000 to $18,000 for recurrent infections.
With an aging population, increasing levels of co-morbidity and widespread use of broad-spectrum antibiotics are predicted to expand the current epidemic of nosocomial CDI. Some of the most troublesome aspects of the current CDI epidemic are the emergence of decreasing effectiveness of the frontline antibiotic metronidizole and the appearance of a more virulent strain of C. difficile with enhanced toxigenic potential which emerges because of floroquinolone resistance. Increasingly, oral vancomycin has become the treatment of choice for nosocomial CDI, though cost and emergence of decreasing effectiveness of vancomycin resistance limit this approach and result in frequent relapses.
Accordingly, as both the incidence and complexity are increasing there is an urgent need for novel therapeutic and prophylactic approaches to CDI. The vaccine disclosed herein provides for local mucosal immune responses in the intestine and meets this unmet need.